The upper respiratory tract is the entrance port for microorganisms entering the lower respiratory tract, i.e., the lungs of a subject. The upper respiratory tract frequently traps these microorganisms and may kill them before they effectively enter the body. However, if the microorganism is able to get a foothold in the upper respiratory tract (e.g., a common cold virus), it is possible that the virus may thereafter move into the lungs. Additionally, the existence or persistence of microorganisms in the upper respiratory tract may lower the immune system so that the lungs become susceptible to another microorganism such as bacteria that may cause a bacterial pneumonia or other infection. Therefore, targeted therapeutic or preventative treatment of the upper respiratory tract would speed the recovery from local infections or preclude the progression to an infection in the lungs or other related systems.
The link between upper respiratory tract infections and the lower respiratory tract is well documented. For example, the following articles, each herein incorporated by reference in their entirety, support the proposition that treating the upper respiratory tract has beneficial value to the lungs and lower respiratory tract. Papadopoulos, et al. “Rhinoviruses infect the lower airways.” J. Infect. Dis. 2000; 181:1875-1884; Gem J. E. “Viral respiratory infection and the link to asthma.” Pediatr. Infect. Dis. J. 2004; 23(Suppl. 1):S78-S86; Fraenkel, et al “Lower airway inflammation during rhinovirus colds in normal and in asthmatic subjects.” Am. J. Respir. Crit. Care Med. 1995: 151:879-886; and Pizzichini, et al. “Asthma and Natural Colds. Inflammatory Indices in Induced Sputum: A Feasibility Study.” Am J. Respir. Crit. Care Med. 1998; 158:1178-84.
The treatment of the upper respiratory tract has focused primarily on traditional pharmaceuticals, such as orally consumed antibiotics. In the 1980's, it was discovered by researchers that the endothelium tissue of the human body produced nitric oxide (NO), and that NO is an endogenous vasodilator, namely, an agent that widens the internal diameter of blood vessels. NO is most commonly known as an environmental pollutant that is produced as a byproduct of combustion. At low concentrations, researchers have discovered that inhaled NO can be used to treat various pulmonary diseases in patients. For example, NO has been investigated for the treatment of patients with increased airway resistance as a result of emphysema, chronic bronchitis, asthma, adult respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD). NO has also been shown to have anti-microbial and/or microcidal activity over a broad range of microorganisms.
While NO has shown promise with respect to certain medical applications, delivery methods and devices must cope with certain problems inherent with gaseous NO delivery. First, exposure to high concentrations of NO maybe toxic, especially exposure to NO in concentrations over 1000 ppm. Even lower levels of NO, however, can be harmful if the time of exposure is relatively high. For example, the Occupational Safety and Health Administration (OSHA) has set respiratory tract exposure limits for NO in the workplace at 25 ppm time-weighted averaged for eight (8) hours.
Another problem with the delivery of NO is that NO rapidly oxidizes in the presence of oxygen to form NO2, which is highly toxic, even at low levels. If the delivery device contains a leak, unacceptably high levels of NO2 gas can develop. In addition, to the extent that NO oxidizes to form NO2, there is less NO available for the desired therapeutic effect. The rate of oxidation of NO to NO2 is dependent on numerous factors, including the concentration of NO, the concentration of O2, and the time available for reaction. Since NO will react with the oxygen in the air to convert to NO2, it is desirable to have minimal contact between the NO gas and the outside environment.
Accordingly, there is a need for a device and method for the topical treatment of upper respiratory tract by the administration of gaseous NO. The delivery must be take into account subject respiration, comfort, and safety. In addition, delivery methods and devices may be designed to target delivery of the NO gas to the upper respiratory region of the patient without allowing the introduction of NO to the lungs.